Towards Interpretable Machine Reading Comprehension with Mixed Effects Regression and Exploratory Prompt Analysis

We investigate the properties of natural language prompts that determine their difficulty in machine reading comprehension tasks. While much work has been done benchmarking language model performance at the task level, there is considerably less literature focused on how individual task items can contribute to interpretable evaluations of natural language understanding. Such work is essential to deepening our understanding of language models and ensuring their responsible use as a key tool in human machine communication. We perform an in depth mixed effects analysis on the behavior of three major generative language models, comparing their performance on a large reading comprehension dataset, and draw some counterintuitive conclusions on the relationship between different prompt features and model accuracy and how that relationship varies between different models. Firstly, we observe a divergence in model accuracy as the prompt’s token count grows with overall stronger models increasing in accuracy and overall weaker models decreasing. Secondly, all models unexpectedly exhibit accuracy gains as they are faced with increasing syntactic complexity – a metric derived from a prompt’s constituency parse tree. Lastly, a post hoc analysis revealed that the overall most difficult prompts had the greatest ability to discriminate between different language models, suggesting their outsized usefulness in MRC evaluation methodologies. These findings raise fascinating questions about the nature of language model understanding and suggest new, more interpretable approaches to their evaluation

The Sunyaev-Zeldovich MITO Project

Compton scattering of the cosmic microwave background radiation by electrons in the hot gas in clusters of galaxies - the Sunyaev-Zeldovich effect - has long been recognized as a uniquely important feature, rich in cosmological and astrophysical information. We briefly describe the effect, and emphasize the need for detailed S-Z and X-ray measurements of nearby clusters in order to use the effect as a precise cosmological probe. This is the goal of the MITO project, whose first stage consisted of observations of the S-Z effect in the Coma cluster. We report the results of these observations.Comment: To appear in Proceedings of `Understanding our Universe at the close of XXth century', School held Apr 25 - May 6 2000, Cargese, 16 pages LaTeX, 2 figures ps (using elsart.sty & elsart.cls), text minor revisio

UCN-01 enhances cytotoxicity of irinotecan in colorectal cancer stem-like cells by impairing DNA damage response

Colorectal cancer (CRC) is one of the most common and lethal cancers worldwide. Despite recent progress, the prognosis of advanced stage CRC remains poor, mainly because of cancer recurrence and metastasis. The high morbidity and mortality of CRC has been recently ascribed to a small population of tumor cells that hold the potential of tumor initiation, i.e. cancer stem cells (CSCs), which play a pivotal role in cancer recurrence and metastasis and are not eradicated by current therapy. We screened CRC-SCs in vitro with a library of protein kinase inhibitors and showed that CRC-SCs are resistant to specific inhibition of the major signaling pathways involved in cell survival and proliferation. Nonetheless, broad-spectrum inhibition by the staurosporin derivative UCN-01 blocks CRC-SC growth and potentiates the activity of irinotecan in vitro and in vivo CRC-SC-derived models. Reverse-Phase Protein Microarrays (RPPA) revealed that, albeit CRC-SCs display individual phospho-proteomic profiles, sensitivity of CRC-SCs to UCN-01 relies on the interference with the DNA damage response mediated by Chk1. Combination of LY2603618, a specific Chk1/2 inhibitor, with irinotecan resulted in a significant reduction of CRC-SC growth in vivo, confirming that irinotecan treatment coupled to inhibition of Chk1 represents a potentially effective therapeutic approach for CRC treatment

Marginal quality of a full-body bulk-fill composite placed with an universal adhesive system in etch-and-rinse and self-etch mode : an in vitrostudy

Marginal seal of a nanohybrid bulk-fill composite compared to a nanohybrid conventional composite, using a universal adhesive (UA) applied in etch-and-rinse (ER) and self-etch (SE) mode was investigated. Thirty-six intact molars were selected and two s

Fluorescence Lifetime Nanoscopy of Liposomal Irinotecan Onivyde: From Manufacturing to Intracellular Processing

: Onivyde was approved by the Food and Drug Administration (FDA) in 2015 for the treatment of solid tumors, including metastatic pancreatic cancer. It is designed to encapsulate irinotecan at high concentration, increase its blood-circulation lifetime, and deliver it to cells where it is enzymatically converted into SN-38, a metabolite with 100- to 1000-fold higher anticancer activity. Despite a rewarding clinical path, little is known about the physical state of encapsulated irinotecan within Onivyde and how this synthetic identity changes throughout the process from manufacturing to intracellular processing. Herein, we exploit irinotecan intrinsic fluorescence and fluorescence lifetime imaging microscopy (FLIM) to selectively probe the supramolecular organization of the drug. FLIM analysis on the manufacturer's formulation reveals the presence of two coexisting physical states within Onivyde liposomes: (i) gelated/precipitated irinotecan and (ii) liposome-membrane-associated irinotecan, the presence of which is not inferable from the manufacturer's indications. FLIM in combination with high-performance liquid chromatography (HPLC) and a membrane-impermeable dynamic quencher of irinotecan reveals rapid (within minutes) and complete chemical dissolution of the gelated/precipitated phase upon Onivyde dilution in standard cell-culturing medium with extensive leakage of the prodrug from liposomes. Indeed, confocal imaging and cell-proliferation assays show that encapsulated and nonencapsulated irinotecan formulations are similar in terms of cell-uptake mechanism and cell-division inhibition. Finally, 2-channel FLIM analysis discriminates the signature of irinotecan from that of its red-shifted SN-38 metabolite, demonstrating the appearance of the latter as a result of Onivyde intracellular processing. The findings presented in this study offer fresh insights into the synthetic identity of Onivyde and its transformation from production to in vitro administration. Moreover, these results serve as another validation of the effectiveness of FLIM analysis in elucidating the supramolecular organization of encapsulated fluorescent drugs. This research underscores the importance of leveraging advanced imaging techniques to deepen our understanding of drug formulations and optimize their performance in delivery applications

Indoor mobility, frailty, and disability in community-dwelling older adults: a mediation model

The general population, but especially older adults, were forced or encouraged to stay home during the recent COVID-19 pandemic. In this context, indoor mobility (IM, the number of steps performed daily at home) may be informative about the general health status of older adults. The present study aimed at evaluating the relationship between IM, frailty (loss of functional reserve including both physical and psychosocial domains), and disability (loss of autonomy measured as activities of daily life, ADLs) in a sample of community-dwelling Italian older adults. Specifically, the primary objective was to investigate IM and disability differences between robust and frail older adults. The secondary objective was to test if frailty is in the causal sequence between IM and disability, i.e., as a mediator in their relationship. Thirty-two participants (mean age = 70 ± 6 years; 56.2% women) were recruited. Frailty and disability were evaluated using the Tilburg Frailty Indicator and the Groningen Activity Restriction Scale, respectively. IM at home was measured via an Adamo wristwatch (a connected accelerometer). One-way analyses of covariance, controlling for age and gender, showed that robust participants, classified according to a score higher than five points in the Tilburg Frailty Indicator, performed significantly more IM (F1,28 = 4.639; p = 0.04) and presented lower disability grade than frail ones (F1,28 = 4.342; p =0.046). Only physical frailty was a mediator in the relationship between IM and disability (F2,29 = 8.538, p < 0.001), with a fully mediated model (z = -2.073, p < 0.04). Conversely, the total frailty score was not a mediator in the same relationship, but with IM accounted for the variance in disability (F2,29 = 8.538, p < 0.001; R2 = 33.7%). Our results suggested that frail older adults restricted their IM more and presented a higher level of disability compared to robust older adults. Moreover, data suggest that IM reduction may have a negative impact on physical frailty and indirectly increase disability

Patient Age Is an Independent Risk Factor of Relapse of Differentiated Thyroid Carcinoma and Improves the Performance of the American Thyroid Association Stratification System

Background: The 2015 American Thyroid Association (ATA) guidelines proposed a three-category system for estimating the risk of recurrence of differentiated thyroid carcinoma (DTC). This system includes several perioperative features, but not age at diagnosis. However, age has traditionally been recognized as a critical factor in the survival of DTC patients, and the eighth edition of TNM stated that patients older than 55 years were at higher risk of death. In this study, we raised the question of whether age at DTC diagnosis impacts on its risk of recurrence. Specifically, the present study aimed to (i) evaluate the association between age at diagnosis and structural recurrence and (ii) investigate whether age at diagnosis could improve the performance of the ATA system. Methods: During the study period, four institutions selected DTC patients treated with both thyroidectomy and radioiodine and who had follow-up for at least one year. Patients with proven structural evidence of disease during follow-up were identified, and disease-free survival (DFS) was calculated accordingly. Results: The study involved 1603 DTC patients with a median age of 49 years and DFS of 44 months. Disease recurred in 8%. The shortest DFS was found in the oldest patients. The Kaplan-Meier curves were calculated for each decade of age, and there was a significant association with DFS (p = 0.0014). Patients older than 55 years had significantly higher risk (hazard ratio [HR] 1.78, 95% confidence interval [CI 1.23-2.56]). The Kaplan-Meier curves of DFS in high-, intermediate-and low-risk groups showed a significant association only in the high-risk group (p = 0.0058). Patients older than 55 years had significantly higher risk of relapse over time only in the high-risk group (HR 2.15 [CI 2.01-4.53]). Cox's proportional analysis showed that the age cutoff of 55 years and the ATA system were significant predictors of relapse. Adding age at diagnosis above 55 years to the ATA system identified a subgroup of patients at highest risk for relapse. Conclusions: The age threshold adopted in the eighth edition of TNM staging system for DTC patients' prognosis also identifies cases at higher risk of relapse. Applying age at diagnosis, with a cutoff of 55 years, to the ATA risk stratification system identifies cases at highest risk of relapse

MITO measurements of the Sunyaev-Zeldovich Effect in the Coma cluster of galaxies

We have measured the Sunyaev-Zeldovich effect towards the Coma cluster (A1656) with the MITO experiment, a 2.6-m telescope equipped with a 4-channel 17 arcminute (FWHM) photometer. Measurements at frequency bands 143+/-15, 214+/-15, 272+/-16 and 353+/-13 GHz, were made during 120 drift scans of Coma. We describe the observations and data analysis that involved extraction of the S-Z signal by employing a spatial and spectral de-correlation scheme to remove a dominant atmospheric component. The deduced values of the thermal S-Z effect in the first three bands are DT_{0} = -179+/-38,-33+/-81,170+/-35 microKelvin in the cluster center. The corresponding optical depth, tau=(4.1+/-0.9) 10^{-3}, is consistent (within errors) with both the value from a previous low frequency S-Z measurement, and the value predicted from the X-ray deduced gas parameters.Comment: Ap.J.Letters accepted, 4 pages, 2 figure

What a difference a workplace makes. A scientometric analysis on the relationship between job crafting and healthy organizations’ factors

Introduction: The transformations that have affected the labour market in recent years have required companies to adapt to fast changes and to keep the pace of global competition. Consequently, workers have been confronted with multiple challenging demands: they have been required to develop flexibility in their jobs and to work faster and better, often with evident costs in terms of performance and their workplace well-being. Given these evidences, as also shown by some of the most recent developments in the field of Positive Work and Organizational Psychology, healthy organizations are those organizations that could resist to these challenges, because they engage in creating an environment that can promote employees’ health and safety, maximising performance. Yet, healthy organizations support positive organizational behaviors through a coherent culture, a positive climate, and good practices. Healthy organizations might also create the conditions to encourage workers to perform job crafting behaviors, meant as proactive individual behaviours aimed at modifying job demands in order to adjust them to personal needs, motivations and talents, thus maximising well-being and performance.Objective: The aim of the study was to overview the state of the art of the debate about the relationship between job crafting and healthy organizations’ factors by performing a scientometric analysis of job crafting. Therefore, the study was aimed to emphasize performances of countries, journals and authors, highlighting the dominant perspectives on the topic.Method: The starting point of the analysis was data recovery from the Scopus database using the term "job crafting" as search criterion within the title, abstract or keywords of the documents retrieved. The analysis was carried out with two softwares, R and VOSviewer, in order to investigate the growth of interest on the topic over the years, the scientific production of countries, journals and authors, the social structure of collaborative network, and the network of keywords.Results: 375 documents about job crafting were retrieved, showing a growing number of publications in recent years, with a preponderance of productions and citations in USA and Netherlands (where the construct was proposed and validated). Cluster analysis performed on the most frequently used keywords showed three main groups, each of them theoretical linked to workplace health: stimulus factors; Job Demands-Resources Model; health dimensions.Discussion: The present bibliometric analysis showed an increasing scientific interest toward job crafting and the importance of specific papers (that opened the two main perspective about it) for the whole research line. Through the cluster analysis of keywords network, it was underlined the relevance of constructs that promote healthy organizations in the scientific production on job crafting.